Pharmacokinetic profile of enrofloxacin and its metabolite ciprofloxacin in Asian house geckos (Hemidactylus frenatus) after single-dose oral administration of enrofloxacin

The pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin were determined following oral administration in 21 Asian house geckos (Hemidactylus frenatus) at a dose of 10 mg/kg. Changes in enrofloxacin and ciprofloxacin plasma concentrations were quantified at regular intervals over 72 h (1, 2, 6, 12, 24, 48, and 72 h). Samples were analysed by high-pressure liquid chromatography (HPLC) and the enrofloxacin pharmacokinetic data underwent a two-compartment analysis. Due to the limited ciprofloxacin plasma concentrations above the lower limit of quantification (LLOQ), the ciprofloxacin data underwent non-compartment analysis and the half-life was determined by the Lineweaver-Burke plot and analysis. The enrofloxacin and ciprofloxacin mean half-lives (t½) were 0.95 h (α) / 24.36 h (β), and 11.06 h respectively, area under the curve (AUC0-24h) were 60.56 and 3.14 µg/mL*h, respectively, maximum concentrations (Cmax) were 12.31 and 0.24 µg/mL, respectively, and time required to reach the Cmax (Tmax) were 1 and 2 h respectively. Enrofloxacin was minimally converted to the active metabolite ciprofloxacin, with ciprofloxacin concentrations contributing only 4.91% of the total fluoroquinolone concentrations (AUC0-24h). Based on the pharmacokinetic indices when using susceptibility breakpoints when determined at mammalian body temperature it is predicted that single oral administration of enrofloxacin (10 mg/kg) would result in plasma concentrations effective against susceptible bacterial species inhibited by an enrofloxacin MIC ≤ 0.5 µg/mL in vitro, but additional studies will be required to determine its efficacy in vivo

Improving mare fertility through dietary intervention: Studies into the effects of nicotinic acid supplementation in vitro and in vivo.

Mare age and reproductive status are thought to be the major drivers of poor reproductive performance, which can result in early embryonic loss rates as high as 20-30%. However, the causes of early embryonic loss are multifactorial and often difficult to establish. Nicotinamide adenine dinucleotide (NAD+) deficiency has recently been implicated in miscarriage and birth defects in women and mice, while NAD+ elevating treatments have resulted in an improvement in oocyte quality from females of advanced maternal age. The aim of this thesis was to investigate the effects of NAD+ precursors on oocyte quality in the mare, opening a potential avenue for improving fertility and reducing early embryo loss in aging mares of high genetic merit. This was achieved through first determining the effects of 3 NAD+ precursors on oocyte quality and embryo development in an appropriate large animal model prior to the determination of the pharmacokinetics of a nicotinic acid supplement in the mare and the ability for the supplement to reach the oocyte in the developing follicle. In order to determine the pharmacokinetics of the NAD+ supplement, an assay for the quantification of various NAD+ metabolites was first developed. This thesis demonstrates that NAD+ biosynthesis is vital to oocyte quality and embryo development in a porcine model, and that nicotinic acid administered as a dietary supplement in mares is rapidly absorbed, metabolised and distributed to cells. Furthermore, supplementation of nicotinic acid over consecutive days of the oestrous cycle in the mare alters the follicular environment in a way that is beneficial for the oocyte. Although further research is needed to fully establish the beneficial effects of NAD+ elevating treatments on oocyte quality and embryo development in the mare, the studies conducted in this thesis have contributed substantially to a more comprehensive understanding of the factors surrounding oocyte quality and early embryonic loss in the mare